Effect of Methylprednisolone on Complement Activation in Patients Undergoing Total Knee-arthroplasty

Osteoarthrosis Clinical Trial

Official title:

Effect of Preoperative Intravenous High Dose Methylprednisolone on Complement Activation in Patients Scheduled for Total Knee-arthroplasty

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02332616
• Other study ID #: HK_VL_08_2014b
• Status: Completed
• Phase: Phase 3
• First received: January 5, 2015
• Last updated: April 7, 2016
• Start date: January 2015
• Est. completion date: April 2016

Study information

• Verified date: April 2016
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Health and Medicines Authority
• Study type: Interventional

Clinical Trial Summary

This study evaluates the pathophysiological effects of a single dose of methylprednisolone administered prior to total knee-arthroplasty surgery. The investigators examine the effect on complement activation.

Half of participants will receive intravenous Solu-Medrol 125 mg, while the other half will receive placebo.

The investigators hypothesize that the group receiving methylprednisolone will experience beneficial inhibition of the undesirable parts of the complement activation.

Description:

The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects on postoperative pain, postoperative nausea and vomiting are well-documented.

Anaesthesia and surgery are associated with a dramatic increase in the inflammatory response. The complement system participates in the disposal of products due to inflammatory damage. The complement activation generates proinflammatory mediators which amplifies the tissue damage and the inflammation.

Glucocorticoid administration prior to surgery is thought to effectively reduce the inflammatory response and the activation of the complement system. The effect of glucocorticoids on specific complement markers after surgery is unknown and calls for further investigation.

This study is embedded in a primary study registrated as: NCT02319343

For further details please view the EudraCT registration:

EudraCT nr.: 2014-003395-23

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years to 80 Years

Eligibility

Inclusion Criteria:

• Osteoarthrosis

• Undergoing total unilateral knee-arthroplasty surgery

• Speak and understand Danish

• Have given informed consent

Exclusion Criteria:

• Revision, bilateral or uni chamber knee-arthroplasty surgery

• General anaesthesia

• Allergy or intolerance towards Methylprednisolone

• Local or systemic infection

• Permanent systemic treatment with steroids within 30 days preoperatively

• Insulin-dependent diabetes

• Active treatment of ulcer within 3 months preoperatively

• Cancer disease

• Autoimmune disease incl. rheumatoid arthritis

• Pregnant or breast feeding women

• Menopause <1 year

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Joint Diseases
• Osteoarthritis
• Osteoarthrosis

Intervention

Drug:
• Methylprednisolone
Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride
• Isotonic Sodium Chloride
Placebo

Locations

Country	Name	City	State
Denmark	Bispebjerg Hospital	Copenhagen NV

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Bispebjerg Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (8)

Abdelmalak BB, Bonilla AM, Yang D, Chowdary HT, Gottlieb A, Lyden SP, Sessler DI. The hyperglycemic response to major noncardiac surgery and the added effect of steroid administration in patients with and without diabetes. Anesth Analg. 2013 May;116(5):1116-22. doi: 10.1213/ANE.0b013e318288416d. Epub 2013 Apr 4. — View Citation

de la Motte L, Kehlet H, Vogt K, Nielsen CH, Groenvall JB, Nielsen HB, Andersen A, Schroeder TV, Lönn L. Preoperative methylprednisolone enhances recovery after endovascular aortic repair: a randomized, double-blind, placebo-controlled clinical trial. Ann Surg. 2014 Sep;260(3):540-8; discussion 548-9. doi: 10.1097/SLA.0000000000000895. — View Citation

Dieleman JM, Nierich AP, Rosseel PM, van der Maaten JM, Hofland J, Diephuis JC, Schepp RM, Boer C, Moons KG, van Herwerden LA, Tijssen JG, Numan SC, Kalkman CJ, van Dijk D; Dexamethasone for Cardiac Surgery (DECS) Study Group. Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. JAMA. 2012 Nov 7;308(17):1761-7. doi: 10.1001/jama.2012.14144. — View Citation

Husted H. Fast-track hip and knee arthroplasty: clinical and organizational aspects. Acta Orthop Suppl. 2012 Oct;83(346):1-39. doi: 10.3109/17453674.2012.700593. Review. — View Citation

Kehlet H. Fast-track hip and knee arthroplasty. Lancet. 2013 May 11;381(9878):1600-2. doi: 10.1016/S0140-6736(13)61003-X. — View Citation

Khan SK, Malviya A, Muller SD, Carluke I, Partington PF, Emmerson KP, Reed MR. Reduced short-term complications and mortality following Enhanced Recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures. Acta Orthop. 2014 Feb;85(1):26-31. doi: 10.3109/17453674.2013.874925. Epub 2013 Dec 20. — View Citation

Malviya A, Martin K, Harper I, Muller SD, Emmerson KP, Partington PF, Reed MR. Enhanced recovery program for hip and knee replacement reduces death rate. Acta Orthop. 2011 Oct;82(5):577-81. doi: 10.3109/17453674.2011.618911. Epub 2011 Sep 6. — View Citation

Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear T, Vender JS, Gray J, Landry E. The effect of single low-dose dexamethasone on blood glucose concentrations in the perioperative period: a randomized, placebo-controlled investigation in gynecologic surgical patients. Anesth Analg. 2014 Jun;118(6):1204-12. doi: 10.1213/ANE.0b013e3182a53981. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in plasma and serum Pentraxin-3 concentrations from baseline (before surgery) to 48 hours after surgery		baseline to 48 hours	No
Secondary	Change in plasma and serum Complement Component 3 concentrations from baseline (before surgery) to 48 hours after surgery		baseline to 48 hours	No
Secondary	Change in plasma and serum Complement Component 4 concentrations from baseline (before surgery) to 48 hours after surgery		baseline to 48 hours	No
Secondary	Change in plasma and serum Mannose-binding lectin concentrations from baseline (before surgery) to 48 hours after surgery		baseline to 48 hours	No
Secondary	Change in plasma and serum Ficolin-1, -2 and -3 concentrations from baseline (before surgery) to 48 hours after surgery		baseline to 48 hours	No
Secondary	Change in plasma and serum Terminal Complement Complex concentrations from baseline (before surgery) to 48 hours after surgery		baseline to 48 hours	No